Factors controlling the development of the reinforcing effects of drugs have been studied with between group designs and rats as subjects. However, there are few studies of such factors with laboratory primates. This may be because acquisition generally is an irreversible process; once something is learned, it cannot be "unlearned." Studies of irreversible processes usually require group designs, and such group-design studies are difficult to conduct with primates. A second problem in studying the acquisition of drug reinforcing effects is that, with the intravenous route, acquisition is so rapid that analysis is difficult. However, with the oral route the development of drug reinforcing effects occurs over a longer period, and this makes it easier to analyze the acquisition process. A research design has been developed that combines two independent strategies: (l) a training protocol that uses a fading procedure to transfer control from an established reinforcer to a potential drug reinforcer, and (2) a testing procedure that permits measurement of control by the novel drug at each step of the acquisition process. This research design will be used to study the development of psychomotor stimulants as orally delivered reinforcers. With the intravenous route a commonly used method to evaluate potential reinforcing effects is to substitute a novel drug for an established drug reinforcer. Substitution procedures are successful with the oral route under some conditions. The proposed studies systematically will examine substitution procedures both before and after the use of the fading procedure to establish drug reinforcing effects. Members of three groups of agents will be studied including psychomotor stimulants, related but ineffective drugs such as fenfluramine, and reinforcing drugs from other pharmacological classes such as phencyclidine, etonitazene, and pentobarbital. The development of effective substitution procedures has both theoretical and practical implications. The practical aspects involve the rapid establishment of new drugs as orally delivered reinforcers and the development of procedures for assessing reinforcing effects in monkeys with a long experimental life. The theoretical aspects include the identification of variables determining the success of substitutions. Knowledge of such variables may be important in understanding how the abuse of one type of drug leads to abuse of other drugs.